Prenatal Alcohol Exposure Affects Vasculature Development in the Neonatal Brain
Prenatal Alcohol Exposure Affects Vasculature Development in the Neonatal Brain
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DOI：
10.1002/ana.23699
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发表时间：
2012-12-01
影响因子：
11.2
通讯作者：
Gonzalez, Bruno Jose
中科院分区：
文献类型：
--
作者：
Jegou, Sylvie;El Ghazi, Faiza;Gonzalez, Bruno Jose
目的：在人类中，产前酒精暴露诱发各种发育障碍，特别是在大脑中。许多研究集中在酒精对神经细胞的有害影响。虽然最近的研究表明，酒精可以影响成人血管生成，产前酒精暴露对大脑microvasculosis.Methods的影响仍然知之甚少：我们使用了小鼠模型，探讨产前酒精暴露对皮质微血管网络在体内和体外的影响和酒精，谷氨酸，血管内皮生长因子A（VEGF）的活动，可塑性和微血管的生存。我们使用定量逆转录聚合酶链反应，蛋白质印迹，免疫组织化学，钙测定，和视频显微镜。我们的特点是产前酒精暴露对人类对照组和胎儿酒精综合征（FAS）/部分FAS（pFAS）患者在不同发育阶段的皮质微血管网络的影响：结果：在小鼠中，产前酒精暴露诱导皮质血管密度的减少，径向方向的微血管的损失，并改变VEGF受体的表达。对脑切片进行的延时实验表明，乙醇抑制谷氨酸诱导的内皮细胞钙动员，影响可塑性，并促进微血管死亡。这些作用被VEGF阻止。在人类中，我们证明了pFAS/FAS胎儿皮质中血管网络的阶段依赖性改变。然而，从妊娠第20周（WG 20）到WG 22没有观察到改变，从WG 30到WG 38，pFAS/FAS患者皮质微血管的径向组织明显改变。解释：产前酒精暴露影响小鼠和pFAS/FAS患者的皮质血管生成，表明血管缺陷导致酒精诱导的脑异常。神经网络2012;72：952-960
Objective: In humans, antenatal alcohol exposure elicits various developmental disorders, in particular in the brain. Numerous studies focus on the deleterious effects of alcohol on neural cells. Although recent studies suggest that alcohol can affect angiogenesis in adults, the impact of prenatal alcohol exposure on brain microvasculature remains poorly understood.Methods: We used a mouse model to investigate effects of prenatal alcohol exposure on the cortical microvascular network in vivo and ex vivo and the action of alcohol, glutamate, and vascular endothelial growth factor A (VEGF) on activity, plasticity, and survival of microvessels. We used quantitative reverse transcriptase polymerase chain reaction, Western blot, immunohistochemistry, calcimetry, and videomicroscopy. We characterized the effect of prenatal alcohol exposure on the cortical microvascular network in human controls and fetal alcohol syndrome (FAS)/partial FAS (pFAS) patients at different developmental stages.Results: In mice, prenatal alcohol exposure induced a reduction of cortical vascular density, loss of the radial orientation of microvessels, and altered expression of VEGF receptors. Time-lapse experiments performed on brain slices revealed that ethanol inhibited glutamate-induced calcium mobilization in endothelial cells, affected plasticity, and promoted death of microvessels. These effects were prevented by VEGF. In humans, we evidenced a stage-dependent alteration of the vascular network in the cortices of fetuses with pFAS/FAS. Whereas no modification was observed from gestational week 20 (WG20) to WG22, the radial organization of cortical microvessels was clearly altered in pFAS/FAS patients from WG30 to WG38.Interpretation: Prenatal alcohol exposure affects cortical angiogenesis both in mice and in pFAS/FAS patients, suggesting that vascular defects contribute to alcohol-induced brain abnormalities. ANN NEUROL 2012;72:952-960